Ultrafast formation of quantized interlayer vibrations in Bi2Se3 by photoinduced strain waves.

This study comprehensively investigated the coherent lattice dynamics in Bi2Se3 by ultrafast optical pump-probe spectroscopy with tunable near-infrared probe pulses. Sample-thickness- and probe-wavelength-dependent experiments revealed the key role of Bi2Se3 optical property in the generation and detection of photoinduced strain waves, whose confinement initiated coherent interlayer vibrations. Furthermore, the frequency and lifetime of the interlayer vibrations could be quantitatively explained with a modified linear chain and an acoustic mismatch model considering elastic coupling at sample-substrate interfaces. The results of this work provide insights for analyzing and interpreting, through ultrafast optical spectroscopy, nanomechanical interactions in layered materials.

Coherent control of interlayer vibrations in Bi2Se3 van der Waals thin-films.

Interlayer vibrations with discrete quantized modes in two-dimensional (2D) materials can be excited by ultrafast light due to the inherent low dimensionality and van der Waals force as a restoring force. Controlling such interlayer vibrations in layered materials, which are closely related to fundamental nanomechanical interactions and thermal transport, in spatial- and time-domain provides an in-depth understanding of condensed matters and potential applications for advanced phononic and photonics devices. The manipulation of interlayer vibrational modes has been implemented in a spatial domain through material design to develop novel optoelectronic and phononic devices with various 2D materials, but such control in a time domain is still lacking. We present an all-optical method for controlling the interlayer vibrations in a highly precise manner with Bi2Se3 as a promising optoelectronic and thermoelasticity material in layered structures using a coherently controlled pump and probe scheme. The observed thickness-dependent fast interlayer breathing modes and substrate-induced slow interfacial modes can be exactly explained by a modified linear chain model including coupling effect with substrate. In addition, the results of coherent control experiments also agree with the simulation results based on the interference of interlayer vibrations. This investigation is universally applicable for diverse 2D materials and provides insight into the interlayer vibration-related dynamics and novel device implementation based on an ultrafast timescale interlayer-spacing modulation scheme.

Interlayer Coupling and Ultrafast Hot Electron Transfer Dynamics in Metallic VSe2/Graphene van der Waals Heterostructures.

Atomically thin vanadium diselenide (VSe2) is a two-dimensional transition metal dichalcogenide exhibiting attractive properties due to its metallic 1T phase. With the recent development of methods to manufacture high-quality monolayer VSe2 on van der Waals materials, the outstanding properties of VSe2-based heterostructures have been widely studied for diverse applications. Dimensional reduction and interlayer coupling with a van der Waals substrate lead to its distinguishable characteristics from its bulk counterparts. However, only a few fundamental studies have investigated the interlayer coupling effects and hot electron transfer dynamics in VSe2 heterostructures. In this work, we reveal ultrafast and efficient interlayer hot electron transfer and interlayer coupling effects in VSe2/graphene heterostructures. Femtosecond time-resolved reflectivity measurements showed that hot electrons in VSe2 were transferred to graphene within a 100 fs time scale with high efficiency. Besides, coherent acoustic phonon dynamics indicated interlayer coupling in VSe2/graphene heterostructures and efficient thermal energy transfer to three-dimensional substrates. Our results provide valuable insights into the intriguing properties of metallic transition metal dichalcogenide heterostructures and motivate designing optoelectronic and photonic devices with tailored properties.

Efficient perovskite solar cells via improved carrier management.

Metal halide perovskite solar cells (PSCs) are an emerging photovoltaic technology with the potential to disrupt the mature silicon solar cell market. Great improvements in device performance over the past few years, thanks to the development of fabrication protocols1-3, chemical compositions4,5 and phase stabilization methods6-10, have made PSCs one of the most efficient and low-cost solution-processable photovoltaic technologies. However, the light-harvesting performance of these devices is still limited by excessive charge carrier recombination. Despite much effort, the performance of the best-performing PSCs is capped by relatively low fill factors and high open-circuit voltage deficits (the radiative open-circuit voltage limit minus the high open-circuit voltage)11. Improvements in charge carrier management, which is closely tied to the fill factor and the open-circuit voltage, thus provide a path towards increasing the device performance of PSCs, and reaching their theoretical efficiency limit12. Here we report a holistic approach to improving the performance of PSCs through enhanced charge carrier management. First, we develop an electron transport layer with an ideal film coverage, thickness and composition by tuning the chemical bath deposition of tin dioxide (SnO2). Second, we decouple the passivation strategy between the bulk and the interface, leading to improved properties, while minimizing the bandgap penalty. In forward bias, our devices exhibit an electroluminescence external quantum efficiency of up to 17.2 per cent and an electroluminescence energy conversion efficiency of up to 21.6 per cent. As solar cells, they achieve a certified power conversion efficiency of 25.2 per cent, corresponding to 80.5 per cent of the thermodynamic limit of its bandgap.

Single-walled carbon-nanotube saturable absorber assisted Kerr-lens mode-locked Tm:MgWO4 laser.

We demonstrate sub-100-fs Kerr-lens mode-locking of a Tm:MgWO4 laser emitting at ∼2µm assisted by a single-walled carbon-nanotube saturable absorber. A maximum average output power of 100 mW is achieved with pulse duration of 89 fs at a pulse repetition rate of ∼86MHz. The shortest pulse duration derived from frequency-resolved optical gating amounts to 76 fs at 2037 nm, corresponding to nearly bandwidth-limited pulses. To the best of our knowledge, these are the shortest pulses generated from any Tm-doped tungstate crystal and the first report on saturable absorber assisted Kerr-lens mode-locking of a Tm laser at ∼2µm.

Spectroscopy and diode-pumped laser operation of transparent Tm:Lu3Al5O12 ceramics produced by solid-state sintering.

A transparent Tm:Lu3Al5O12 ceramic is fabricated by solid-state reactive sintering at 1830 °C for 30 h using commercial α-Al2O3 and Lu2O3/Tm2O3 powders and sintering aids - MgO and TEOS. The ceramic belongs to the cubic system and exhibits a close-packed structure (mean grain size: 21 µm). The in-line transmission at ∼1 µm is 82.6%, close to the theoretical limit. The spectroscopic properties of the ceramic are studied in detail. The maximum stimulated-emission cross-section is 2.37×10-21 cm2 at 1749nm and the radiative lifetime of the 3F4 state is about 10 ms. The modified Judd-Ofelt theory accounting for configuration interaction is applied to determine the transition probabilities of Tm3+, yielding the intensity parameters Ω2 = 2.507, Ω4 = 1.236, Ω6 = 1.340 [10-20 cm2] and α = 0.196×10-4 cm. The effect of excited configurations on lower-lying interconnected states with the same J quantum number is discussed. First laser operation is achieved under diode-pumping at 792 nm. A 4 at.% Tm:Lu3Al5O12 ceramic laser generated 3.12 W at 2022-2035nm with a slope efficiency of 60.2%. The ceramic is promising for multi-watt lasers at >2 µm.

Amphiphilic siRNA Conjugates for Co-Delivery of Nucleic Acids and Hydrophobic Drugs.

Combination therapy of nucleic acids and chemical drugs for cancer treatment is a promising strategy to enhance the therapeutic efficacy by simultaneously regulating multiple troublesome pathways. In this study, we report on polyethylene glycol-siRNA-polycaprolactone (PEG-siRNA-PCL) micelles that encapsulate hydrophobic drugs for efficient co-delivery of siRNA and drugs to cancer cells. Amphiphilic PEG-siRNA-PCL copolymers were synthesized by annealing antisense siRNA-PCL conjugates with sense siRNA-PEG conjugates. After paclitaxel encapsulation, PEG-siRNA-PCL micelles containing antiapoptotic Bcl-2-specific siRNA were stabilized with linear polyethylenimine via electrostatic interactions. Stabilized PEG-siRNA-PCL micelles showed superior anticancer effects, assessed by caspase-3 activity analysis, apoptotic cell staining, and a cytotoxicity test, to those of paclitaxel-free PEG-siRNA-PCL micelles and unmodified siRNAs. The strong anticancer activity of paclitaxel-incorporated siRNA micelles can be attributed to the synergistic effect of Bcl-2 siRNA and paclitaxel. This work provides an efficient co-delivery platform for combination anticancer therapy with siRNA and chemotherapy.

Tumor-targeted delivery of paclitaxel using low density lipoprotein-mimetic solid lipid nanoparticles.

Water-insoluble anticancer drugs, including paclitaxel, present severe clinical side effects when administered to patients, primarily associated with the toxicity of reagents used to solubilize the drugs. In efforts to develop alternative formulations of water-insoluble anticancer drugs suitable for intravenous administration, we developed biocompatible anticancer therapeutic solid lipid nanoparticles (SLNs), mimicking the structure and composition of natural particles, low-density lipoproteins (LDLs), for tumor-targeted delivery of paclitaxel. These therapeutic nanoparticles contained water-insoluble paclitaxel in the core with tumor-targeting ligand covalently conjugated on the polyethylene glycol (PEG)-modified surface (targeted PtSLNs). In preclinical human cancer xenograft mouse model studies, the paclitaxel-containing tumor-targeting SLNs exhibited pronounced in vivo stability and enhanced biocompatibility. Furthermore, these SLNs had superior antitumor activity to in-class nanoparticular therapeutics in clinical use (Taxol and Genexol-PM) and yielded long-term complete responses. The in vivo targeted antitumor activities of the SLN formulations in a mouse tumor model suggest that LDL-mimetic SLN formulations can be utilized as a biocompatible, tumor-targeting platform for the delivery of various anticancer therapeutics.

Low-density lipoprotein-mimicking nanoparticles for tumor-targeted theranostic applications.

This study introduces multifunctional lipid nanoparticles (LNPs), mimicking the structure and compositions of low-density lipoproteins, for the tumor-targeted co-delivery of anti-cancer drugs and superparamagnetic nanocrystals. Paclitaxel (4.7 wt%) and iron oxide nanocrystals (6.8 wt%, 11 nm in diameter) are co-encapsulated within folate-functionalized LNPs, which contain a cluster of nanocrystals with an overall diameter of about 170 nm and a zeta potential of about -40 mV. The folate-functionalized LNPs enable the targeted detection of MCF-7, human breast adenocarcinoma expressing folate receptors, in T2 -weighted magnetic resonance images as well as the efficient intracellular delivery of paclitaxel. Paclitaxel-free LNPs show no significant cytotoxicity up to 0.2 mg mL(-1) , indicating the excellent biocompatibility of the LNPs for intracellular drug delivery applications. The targeted anti-tumor activities of the LNPs in a mouse tumor model suggest that the low-density lipoprotein-mimetic LNPs can be an effective theranostic platform with excellent biocompatibility for the tumor-targeted co-delivery of various anti-cancer agents.

Cross-linked iron oxide nanoparticles for therapeutic engineering and in vivo monitoring of mesenchymal stem cells in cerebral ischemia model.

Poly(ethylene glycol)-coated cross-linked iron oxide nanoparticles (PCIONs) are developed for therapeutic engineering of mesenchymal stem cells (MSCs) and their monitoring via magnetic resonance (MR) imaging at a time. PCIONs successfully combine with plasmid DNA (pDNA) via ionic interaction. Accordingly, PCION/pDNA complexes mediate superior translocations of vascular endothelial growth factor (VEGF) pDNA into intracellular regions of MSCs under external magnetic field, which significantly elevate production of VEGF from MSCs. Genetically engineered MSCs are also clearly visualized via MR imaging after administration to rat cerebrovascular ischemia models, which enable tracking of MSCs migration from injected sites to injured ischemic area.

Chitosan-g-hematin: enzyme-mimicking polymeric catalyst for adhesive hydrogels.

Phenol derivative-containing adhesive hydrogels has been widely recognized as having potential for biomedical applications, but their conventional production methods, utilizing a moderate/strong base, alkaline buffers, the addition of oxidizing agents or the use of enzymes, require alternative approaches to improve their biocompatibility. In this study, we report a polymeric, enzyme-mimetic biocatalyst, hematin-grafted chitosan (chitosan-g-hem), which results in effective gelation without the use of alkaline buffers or enzymes. Furthermore, gelation occurs under mild physiological conditions. Chitosan-g-hem biocatalyst (0.01%, w/v) has excellent catalytic properties, forming chitosan-catechol hydrogels rapidly (within 5 min). In vivo adhesive force measurement demonstrated that the hydrogel formed by the chitosan-g-hem activity showed an increase in adhesion force (33.6 ± 5.9 kPa) compared with the same hydrogel formed by pH-induced catechol oxidation (20.6 ± 5.5 kPa) in mouse subcutaneous tissue. Using the chitosan-g-hem biocatalyst, other catechol-functionalized polymers (hyaluronic acid-catechol and poly(vinyl alcohol)-catechol) also formed hydrogels, indicating that chitosan-g-hem can be used as a general polymeric catalyst for preparing catechol-containing hydrogels.

Ischemic brain imaging using fluorescent gold nanoprobes sensitive to reactive oxygen species.

Fluorescein-labeled hyaluronic acids (HA) were immobilized on gold nanoparticles for reactive oxygen species (ROS) detection. The efficacy of HA immobilized gold nanoparticles (HHAuNPs) was evaluated in a stroke animal model. The stroke rat model was produced by transient middle cerebral artery occlusion (MCAO), which induced transient ischemia and reperfusion (I/R) in the brain. The increase of ROS in the I/R brain was confirmed by TBARS assay with the brain extracts. For brain imaging, HHAuNPs were injected into the rat brain 1 h before transient MCAO. Five hours after the injection, the rats were sacrificed and the brains were subjected to imaging analysis. The results showed that stronger signals were detected in the I/R brains than in the normal brains. To identify the time window for effective detection of ROS, HHAuNPs were injected into the post-ischemic rat brains at various time points. The results showed that ROS level reached a maximum at 24 h after the transient MCAO. Also, a live imaging study was performed with HHAuNPs in the normal and I/R animals. The results confirmed that ROS level increased in the I/R animal group with time, while the signal was decreased in the normal animal group. Together, our results suggest that HHAuNPs may be useful to monitor ROS level in the ischemic brain and to identify the infarct areas in ischemic brains for the treatment of stroke.

Stabilized calcium phosphate nano-aggregates using a dopa-chitosan conjugate for gene delivery.

Calcium phosphate (CAP) has a wide range of applications in biomedical systems. Although there is great potential for the use of CAP in the development of gene delivery systems, the uncontrollable growth of CAP crystal makes it difficult to use in a practical nano-gene delivery system. The purpose of this study was to develop nano-sized CAP particles containing nucleic acids (e.g. DNA, siRNA). The CAP nano-aggregates (CAP/pDNA/dopa-Chi) were successfully prepared by serial addition of plasmid DNA (pDNA) and dopa (3,4-dihydroxy-L-phenylalanine) modified chitosan to growing CAP particles in calcium phosphate solution. The addition of the dopa moiety is thought to enable chitosan adsorption onto the surface of forming calcium phosphate particles to prevent further growth. The CAP/pDNA/dopa-Chi significantly increased the serum stability of pDNA, and showed high cellular uptake efficiency and trans-gene expression. Additionally, the chitosan stabilized CAP nano-aggregates were also prepared for siRNA delivery (CAP/siRNA/dopa-Chi) via the same method as for CAP/pDNA/dopa-Chi. A notable siRNA gene silencing effect of CAP/siRNA/dopa-Chi was exhibited without any sign of cytotoxicity.

Protein-resistant, reductively dissociable polyplexes for in vivo systemic delivery and tumor-targeting of siRNA.

Small interfering RNA (siRNA) has been considered as a very attractive therapeutic alternative to chemical drugs; however, the chemical and biological instability and poor delivery efficiency of siRNA limit its success in clinical applications. Here we report a protein-resistant, reductively dissociable siRNA delivery system based on self-assembled polyelectrolyte complexes of dextran-siRNA conjugates linked by disulfide bonds. The prepared polyplexes exhibit excellent dispersion stability in the presence of serum because of the anti-fouling property of dextran exposed onto the complex surface. The enzymatic degradation of siRNA is also effectively suppressed within the complex. Folates are introduced as an active tumor-targeting moiety via the conjugation of folates to the hydroxyl groups of dextran. An in vivo investigation with a xenograft tumor mouse model shows that the folate-decorated dextran-siRNA conjugates are very efficiently targeted to cancer cells and induce sequence-specific gene silencing.

Optically traceable solid lipid nanoparticles loaded with siRNA and paclitaxel for synergistic chemotherapy with in situ imaging.

Here, we report quantum dot-incorporating solid lipid nanoparticles (SLNs) for anticancer theranostics with synergistic therapeutic effects of paclitaxel-siRNA combination. The natural components of a low-density lipoprotein (LDL) are reconstituted to produce LDL-mimetic SLNs having a stable core/shell nanostructure incorporating quantum dots and paclitaxel within the lipid shell while anionic siRNA molecules are electrostatically complexed with the outer surface of SLNs. The produced SLN/siRNA complexes efficiently deliver both of paclitaxel and Bcl-2 targeted siRNA into human lung carcinoma cells and exhibit synergistic anticancer activities by triggering caspase-mediated apoptosis as determined by median effect plot analysis. Moreover, the strong fluorescence from quantum dots within SLNs enables in situ visualization of intracellular translocation of SLNs into cancer cells. Our study suggests that LDL-mimetic SLNs can be utilized as a multifunctional and optically traceable nanocarrier for efficient anticancer theranostics.

Thermally controlled wettability of a nanoporous membrane grafted with catechol-tethered poly(N-isopropylacrylamide).

A nanoporous membrane is coated with catechol-tethered poly(N-isopropylacrylamide). The thermosensitive variation of surface wettability determines the hindered diffusivity of dextran (40 kDa) through the nanopores.

Prolonged gene silencing by siRNA/chitosan-g-deoxycholic acid polyplexes loaded within biodegradable polymer nanoparticles.

Recently, small interfering RNA (siRNA) has received much attention for therapeutic applications; however, low transfection efficiency and intrinsic instability limit effective gene silencing. Here we show a new approach based on the incorporation of siRNA/polyelectrolyte complexes into biodegradable poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles to stabilize siRNA within a hydrophobic solid matrix for prolonged gene silencing. To solubilize siRNA in organic media, chitosan oligosaccharides grafted with deoxycholic acids are synthesized and complexed with siRNA, generating a self-assembled polyelectrolyte complex of 123.9 ± 56.8 nm in diameter. The complex is mixed with PLGA solution and emulsified in water to prepare siRNA-loaded PLGA nanoparticles having a diameter of about 230 nm. The excellent structural stability of the prepared nanoparticles leads to efficient cellular uptake followed by effective gene silencing even in the presence of serum proteins. These results suggest that the encapsulation of siRNA into biodegradable polymer matrix can be an effective means of improving the structural stability of siRNA for prolonged therapeutic efficacy.

Chitosan oligosaccharide-stabilized ferrimagnetic iron oxide nanocubes for magnetically modulated cancer hyperthermia.

Magnetic nanoparticles have gained significant attention as a therapeutic agent for cancer treatment. Herein, we developed chitosan oligosaccharide-stabilized ferrimagnetic iron oxide nanocubes (Chito-FIONs) as an effective heat nanomediator for cancer hyperthermia. Dynamic light scattering and transmission electron microscopic analyses revealed that Chito-FIONs were composed of multiple 30-nm-sized FIONs encapsulated by a chitosan polymer shell. Multiple FIONs in an interior increased the total magnetic moments, which leads to localized accumulation under an applied magnetic field. Chito-FIONs also exhibited superior magnetic heating ability with a high specific loss power value (2614 W/g) compared with commercial superparamagnetic Feridex nanoparticles (83 W/g). The magnetically guided Chito-FIONs successfully eradicated target cancer cells through caspase-mediated apoptosis. Furthermore, Chito-FIONs showed excellent antitumor efficacy on an animal tumor model without any severe toxicity.

Small-interfering RNA (siRNA)-based functional micro- and nanostructures for efficient and selective gene silencing.

Because of RNA's ability to encode structure and functional information, researchers have fabricated diverse geometric structures from this polymer at the micro- and nanoscale. With their tunable structures, rigidity, and biocompatibility, novel two-dimensional and three-dimensional RNA structures can serve as a fundamental platform for biomedical applications, including engineered tissues, biosensors, and drug delivery vehicles. The discovery of the potential of small-interfering RNA (siRNA) has underscored the applications of RNA-based micro- and nanostructures in medicine. Small-interfering RNA (siRNA), synthetic double-stranded RNA consisting of approximately 21 base pairs, suppresses problematic target genes in a sequence-specific manner via inherent RNA interference (RNAi) processing. As a result, siRNA offers a potential strategy for treatment of many human diseases. However, due to inefficient delivery to cells and off-target effects, the clinical application of therapeutic siRNA has been very challenging. To address these issues, researchers have studied a variety of nanocarrier systems for siRNA delivery. In this Account, we describe several strategies for efficient siRNA delivery and selective gene silencing. We took advantage of facile chemical conjugation and complementary hybridization to design novel siRNA-based micro- and nanostructures. Using chemical crosslinkers and hydrophobic/hydrophilic polymers at the end of siRNA, we produced various RNA-based structures, including siRNA block copolymers, micelles, linear siRNA homopolymers, and microhydrogels. Because of their increased charge density and flexibility compared with conventional siRNA, these micro- and nanostructures can form polyelectrolyte complexes with poorly charged and biocompatible cationic carriers that are both more condensed and more homogenous than the complexes formed in other carrier systems. In addition, the fabricated siRNA-based structures are linked by cleavable disulfide bonds for facile generation of original siRNA in the cytosol and for target-specific gene silencing. These newly developed siRNA-based structures greatly enhance intracellular uptake and gene silencing both in vitro and in vivo, making them promising biomaterials for siRNA therapeutics.

Cationic lipid-coated gold nanoparticles as efficient and non-cytotoxic intracellular siRNA delivery vehicles.

PURPOSE: Cationic lipid-coated gold nanoparticles were developed for efficient intracellular delivery of therapeutic siRNA. METHODS: Particle formation was characterized by UV-visible spectroscopy, atomic force microscopy, and dynamic light scattering analysis. Cellular uptake, gene silencing effect, and cytotoxicity were investigated in multiple human cancer cell lines. RESULTS: Nanoparticles had a spherical nanostructure with highly cationic surface charge and could form stable nanosized polyelectrolyte complexes with siRNA via electrostatic interactions; complexes exhibited efficient intracellular uptake and significant gene silencing effect with markedly low cytotoxicity compared to the widely used polycationic carrier, linear polyethyleneimine. CONCLUSIONS: We demonstrated that cationic lipid-coated gold nanoparticles could be widely utilized as efficient and safe siRNA nanocarriers for diverse therapeutic and diagnostic applications.